Possible contribution of hepatocyte secretion to the elevation of plasma exosomal arginase-1 in high-fat diet-fed mice
Possible contribution of hepatocyte secretion to the elevation of plasma exosomal arginase-1 in high-fat diet-fed mice
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DOI：
10.1016/j.lfs.2021.119588
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发表时间：
2021-05-06
期刊：
影响因子：
6.1
通讯作者：
Ogino, Keiki
中科院分区：
文献类型：
--
作者：
Ogino, Noriyoshi;Takahashi, Hidekazu;Ogino, Keiki
目的：血管组织精氨酸酶的升高降低了一氧化氮的产生，这被认为是肥胖动脉粥样硬化的早期步骤。先前，我们发现精氨酸酶同工酶之一精氨酸酶-1在肥胖成人血浆中升高。本研究的目的是阐明肥胖增加血液中精氨酸酶-1水平的机制。主要方法：分析C57/BL6J雄性小鼠饲喂高脂饲料12周后一氧化氮/精氨酸代谢及血浆外泌体的相关因素。为了探索精氨酸酶的分泌器官，我们分析了精氨酸酶在不同器官中的表达水平。为了进一步研究血浆、血糖水平与肝脏精氨酸酶-1水平的关系，我们分析了高糖治疗后的人肝癌细胞系HepG2。主要发现：饲喂hfd的小鼠血浆精氨酸酶活性的增加与血糖水平呈正相关，并伴有外泌体精氨酸酶-1水平的增加。在精氨酸酶高表达的器官中，饲喂hfd的小鼠肝脏中精氨酸酶-1显著升高。高糖暴露使HepG2细胞外泌体和总裂解物中精氨酸酶-1的表达增加。意义：血浆外泌体精氨酸酶-1升高有助于肥胖患者血浆精氨酸酶活性升高。肝脏是外泌体精氨酸酶-1分泌到血浆的候选器官，高葡萄糖水平诱导的p38途径可能参与其中。
Aims: The elevation of arginase in vascular tissues decreases nitric oxide production, which is considered as an early step of atherosclerosis in obesity. Previously, we found that arginase-1, one of arginase isozymes, was elevated in the blood plasma of obese adults. The purpose of this study is to elucidate the mechanism by which obesity increases arginase-1 levels in the blood. Main methods: C57/BL6J male mice fed a high-fat diet (HFD) for 12 weeks were analyzed for factors related to nitric oxide/arginine metabolism and plasma exosomes. To explore the arginase secretory organs, the protein expression levels were analyzed in several organs. To further investigate the relationship between exosomal arginase-1 in plasma, blood glucose levels and arginase-1 in the liver, HepG2 (the human hepatoma cell line) was analyzed after treatment with high glucose. Key findings: The increase in arginase activity in the plasma of HFD-fed mice was positively corelated with blood glucose levels and was accompanied by an increase in exosomal arginase-1 levels. Among the organs that highly express arginase, the liver of HFD-fed mice showed a significant increase in arginase-1. The expression of arginase-1 in exosomes and total lysates of HepG2 cells were increased by high glucose exposure. Significance: Increased exosomal arginase-1 in plasma contributes to increased plasma arginase activity in obesity. The liver is a candidate organ for the secretion of exosomal arginase-1 into plasma, and the p38 pathway induced by high glucose levels may be involved.